Endocrinology

what are 2 types of cell to cell communication?

1\.) direct: using tight junctions

2\.) indirect via chemical messenger

what are 3 types of chemical messenger signalling?

1\.) paracrine: short distance traversed

2\.) neurotransmitters: secretory cell is neuron, neurotransmitter traverses synpase and binds receptor

3\.) hormones: travels long distances through blood vessels

for signalling of the nervous system; what is the message, travel location and target?

message: neurotrasmitters

travels in: synapse

target: neurons, muscles and glands

for signalling of the endocrine system, what is the message, travel location and target?

message: hormones

travels in: bloodstream

target: most cell types with correct receptor on it

what 2 cell types does the endocrine system consist of?

1\.) endocrine cells: secrete hormones

2\.) target cells: have receptors for hormone

what are the 10 primary endocrine organs?

1\.) pineal gland

2\.) hypothalamus

3\.) pituitary gland

4\.) thyroid gland

5\.) parathyroid glands

6\.) thymus

7\.) adrenal gland

8\.) pancreas

9\.) ovaries/testes

10\.) placenta

what are the 6 secondary endocrine organs?

1\.) skin

2\.) heart

3\.) small intestine

4\.) kidney

5\.) liver

6\.) stomach

what are 4 things that can regulate hormone secretion?

1\.) neurotransmitters

2\.) other hormones

3\.) metabolites

4\.) ions

what are the 5 functions of the endocrine system?

1\.) metabolism

2\.) growth and development

3\.) reproduction

4\.) response to stress

5\.) water and electrolyte balance

what are hydrophobic hormones?

steroid and thyroid hormones

poorly soluble

travel in blood bound to carrier proteins

can cross lipid bilayer

receptor in cytosol or nucleus

often have cholesterol as a precursor to its synthesis

what are hydrophilic hormones?

peptides and catecholamines

water soluble

travel freely in blood

cannot cross lipid bilayer

receptor on membrane

often synthesized in organelles and stored in secretory vesicles

what are the 5 steps of hydrophobic signalling?

1\.) hormone diffuses into cell

2\.) binds receptor

3\.) hormone receptor complex binds hormone response element (HRE) on DNA

4\.) mRNA coding for specific protein is made

5\.) specific protein made in cytosol

what are the 6 steps of the cAMP second messenger pathway?

1\.) hormone binds receptor on plasma membrane

2\.) G protein is activated

3\.) activity of adenylate cyclase increases

4\.) cAMP synthesized

5\.) protein kinase A is activated

6\.) cellular proteins are phosphorylated

how does caffeine affect the cAMP second messenger pathway?

caffeine prolongs cAMP activity

inhibits the phosphodiesterase that usually degrades cAMP

antagonist to the adenosine receptor which normally would inhibit neural activity

what is the infundibulum?

a tissue bridge that connects the hypothalamus and pituitary gland

what are the 2 types of control of hormone secretion by neurons of the autonomic nervous system?

1\.) targets the adrenal medulla, agonist to release hormone (epinephrine)

2\.)target endrocrine gland cell, synapse in PNS at autonomic ganglion, agonist or antagonist to hormone release

what are the 2 types of control of hormone secretion by neurons of the hypothalamus?

1\.) targets anterior pituitary by release of hormones in the CNS agonizing or antagonizing the anterior pituitary to release hormones

2\.) targets the posterior pituitary and directly releases hormones

what structures are present for hypothalamus and pituitary connection?

median eminence at hypothalamus base contains important blood vessels

paraventricular nuclei in hypothalamus go to posterior pituitary

specific nuclei in hypothalamus go to medan eminence

arterial blood supply for anterier pituitary gland starts at infundibulum

what are sources of blood supply provided to the pituitary gland?

hypothalamo-hypophyseal portal vessels supply blood to anterior pituitary

posterior pituitary recieves its own arterial blood supply which then flows into anterior pituitary

both anterior and posterior pituitary deoxygenated blood go to venous circulation and heart

what are the 2 types of nuclei that go from the hypothalamus to the posterior pituitary?

1\.) supraoptic nucleus: cells secrete oxytocin

2\.) paraventricular nucleus: cells secrete ADH

what are the effects of antidiuretic hormone?

also called vasopressin

conserves body water and blood volume by increasing kidney reabsorption

increases blood pressure by constricting arteries and arterioles

what are the 4 steps of ADH effect on the kidneys?

1\.) ADH leaves peritubular capillary and binds ADH receptor on cell membrane

2\.) G protein signalling cascade

3\.) PKA phosphorylates aquaporin containing vesicles

4\.) aquaporins imbed in apical membrane to facilitate water reuptake

what effects does low blood pressure and high plasma osmolarity have on ADH release, and how is it detected?

low BP: increase ADH release; detected by reduced stretch of atria walls and aortic and carotid arteries

high plasma osmolarity: increase ADH release; detected by osmoreceptors in hypothalamus

what is the effect and regulation of oxytocin with respect to childbirth?

effect: stimulate uterine contactions to aid labour

regulation: response to stretch of uterine neck by fetus

what is the effect and regulation of oxytocin with respect to nursing?

effect: smooth muscle contraction in breast tissue for milk let down

regulation: response to suckling

what is the hypothalamic pituitary portal system?

neurosecretory cells release hypothalamic hormones into capillary bed

hormones travel by portal system to anterior pituitary

exchange between blood and tissues occurs at capillaries

what is the feedback system between the hypothalamus, anterior pituitary and target gland?

hormone 3 released by target gland inhibits both the anterior pituitary and hypothalamus

what is the hormone release process for the final release of cortisol?

hypothalamus: produces corticotropin releasing hormone

anterior pituitary: releases adrenocorticotropic hormone

target: released cortisol

what is the epiphyseal plate?

site of growth in length of bone

cartilage between epiphysis (ball shape at bone ends) and diaphysis(bone shaft)

target cells for action of GH and IGF-1 are chondrocyctes

what are osteoblasts?

provide collagen and proteoglycans to make the osteoid

bone makers

what are osteocytes?

mature osteoblasts that are surrounded by bone matrix

bone maintainers

spread nutrients and oxygen to other cells

what are osteoclasts?

responsible for resorption or breakdown of bone

bone breakers

secrete acids and enzymes

what is the organic/inorganic bone makeup?

35% organic: collagen and proteoglycans

65% inorganic: calcium phosphate crystals (hydroxypatite)

without inorganic compounds bones would be too flexible, without collagen bones would be too brittle

what is the role of IGF-1 in bone development?

supplied by liver and bone

stimulate chondroye cell division- hyperplasia

what is the process of bone growth?

chondrocytes produce new cartilage in epipjyseal plate

epiphyseal plate widens causing bone to lenghten

chondrocytes die

osteoblasts replace chondrocytes to lay down bone

epiphyseal plate closes at puberty, affected by sex hormones, no further increase in length

what are the 4 steps of bone rebuilding following a fracture?

1\.) blood escapes ruptured bone causing hematoma

2\.)tissue repair begins with fibrocartilaginous callus forming between ends of broken bone

3\.)osteoblasts produce trabeculae of spongy bone and convert fibrocartilage callus to bony callus, joining bone

4\.) osteoblasts build new compact bone at periphery and osteoclasts absorb spongy bone creating a medullary cavity

what is the growth hormone feedback system?

hypothalamus stimulates anterior pituitary with GHRH, but inhibits it with SST

anterior pituitary stimulates its target gland with GH

target gland secretion inhibits GH and GHRH synthesis, but activates SST

what are 4 stimulators of growth hormone release?

1\.) sleep

2\.) exercise

3\.) stress

4\.) low blood glucose

what is hyperplasia vs hypertrophy?

plasia: increase cell number

trophy: increase cell size

what are actions of growth hormone/ insulin-like growth factors?

promote hypertrophy and hyperplasia

stimulate lipolysis in adipose tissue

stimulate gluconeogenesis in liver

stimulate protein synthesis in muscle

increase uptake of amino acids into cells

inhibit glucose uptake in adipose tissue and skeletal muscle

what is acromegaly vs gigantism?

acromegaly: too much growth hormone after epiphysis

gigantism: too much growth hormone before epiphysis

what are 5 functions of calcium?

1\.) bone and teeth structure

2\.) muscle contraction

3\.) heart contraction

4\.) vesicle release

5\.) blood clotting

how is calcium stored in bone?

stores as hydroxyapatite

osteoblasts add calcium to bone

osteoclasts release calcium from bone into the blood

what 3 hormones control plasma calcium levels? what are the 3 target sites?

1\.) parathyroid hormone

2\.) calcitriol (also called 1,25-dihydroxycholecalciferol)

3\.) calcitonin

acts on bones, kidneys and digestive tract

what is parathyroid hormone?

stimulated by low plasma calcium concentrations

stimulates bone resorption

in kidneys: increases calcium reabsorption, decreases phosphate reabsorption, stimulates calcitriol synthesis causing increased calcium absorption from GI

what is hyperparathyroidism?

excess secretion of PTH

causes tumors or hyperfunction of parathyroid glands

leads to vitamin D3 deficiency or chronic kidney disease

causes deposition of calcium based salts like kidney stones

bones may be painful and fracture

can lead to lethargy, fatigue, depression

hypertension and heart palpitations

what is hypoparathyroidism?

inadequate secretion of PTH

causes trauma to parathyroid glands, autoimmune damage, congenital malformation

PTH resistance can occur if blood calcium concentration is low but PTH is high

neuromuscular hyperexcitability

causes muscle tingling, spasms and stiffening

abnormal heart rhythms

what is calcitriol?

increases calcium absorption in GI

increases calcium reabsorption in kidney

vitamin D from skin and GI ingested where it converts to 25-hydroxylase in the liver

PTH stimulates 1-hydroxylase to combine with 25-hydroxylase in kidneys

what are effects of vitamin D deficiency?

rickets in children, osteomalacia in adults

bone softening

deficient mineralization

increases risk of colon, breast, prostate and ovarian cancer

increases risk of some autoimmune diseases

what is calcitonin?

from C cells of thyroid gland

peptide hormone (hydrophilic)

triggered by high plasma concentration

reduces activity of osteoclasts

inhibit calcium reabsorption in kidneys

protect skeleton from calcium loss during pregnancy and lactation

what is osteoporosis?

porous bone

decreased bone mass leading to bone fragility and increased fracture risk

can be prevented with a diet rich in calcium and vitamin D, exercise, and avoiding smoking and alcohol

what are treatment options for osteoporosis?

calcium and vitamin D supplements

bisphosphates to inhibit osteoclast activity

estrogen/hormone therapy

estrogen receptor modulators

calcitonin

parathyroid hormone

denosumab which inhibits a downstream effector of PTH

what stimulates thyroid hormone secretion in infants?

cold temperatures

what 2 factors inhibit thyroid hormone secretion?

1\.) stress

2\.) warmth

what are features of thyroid follicles?

made of internal colloid and outer follicular cell

what does the thyroid colloid contain?

thyroglobulin (protein): precursor for thyroid hormones, contains tyrosine residues

enzymes

iodine

how are thyroid hormones synthesized?

1\.) iodide is cotransported with sodium to interstitial fluid

2\.) iodide diffuses through follicle cell into colloid

3\.) iodide is oxidized to iodine and attached to rings of tyrosines in thyroglobulin (formation of di-iodotyrosine and mono-iodotyrosine)

4\.) iodinated ring of one MIT or DIT is added to a DIT at another spot

5\.) thyroglobulin endocytosed containing T3 and T4

6\.) lysosomal enzymes release T3 and T4 from TG

7\.)T3 and T4 secreted in interstitial fluid

what is T3 vs T4?

T3: MIT and DIT (contains 3 iodines)

T4: DIT and DIT (contains 4 iodines)

how does thyroid stimulating hormone aid in the release of T3 and T4?

TSH binding TSH receptor causing cAMP signalling cascade which aids in vesicle formation of T3 and T4 in follicle

what is the function of thyroxine binding globulin and albumin?

both carrier proteins of T3 and T4

synthesized in liver

TBG: high affinity, low capacity

albumin: non-specific plasma protein, low affinity but in excess has high capacity

what are the following thyroid hormones: T4, T3, RT3?

T4: most abundant, converted to T3 in tissues by deiodinases

T3: more active than T4

RT3: inactive thyroid hormone, T4 converted to it by D3

what are the functions of T3 and T4?

regulate basal metabolic rate

necessary for growth, brain development

promotes energy mobilization

increases number of beta adrenergic receptors

what is hyperthyroidism?

thyroid hormone excess

caused by tumors, or thyroid stimulating immunoglobulins (grave’s disease)

causes nervousness, insomnia, high heart rate, eye disease and weight loss

what is grave’s disease?

an autoimmune disease where abnormal antibodies against TSH receptor are produced

most common cause of hyperthyroidism

most common cause of general thyroid enlargement

thyroid stimulating immunoglobulins agonize TSH receptor causing increased in TH but decreased TSH

what is hypothyroidism?

thyroid hormone deficiency

caused by lack of iodine or an under active thyroid

causes lethargy, fatigue, cold intolerance, weakness, hair loss and weight gain

what are consequences of iodine deficiency?

goiter may be present

leaves thyroid gland unable to produce T3 or T4

lack of negative feedback causes excess TSH

TSH stimulates growth of thyroid gland by enhancing follicular cell division

uncommon in developed world from iodinized salt

leading cause of preventable intellectual disability

what are the 4 layers of adrenal glands? what does each secrete?

1\.) medualla: epinephrine and norepinephrine

2\.) zona reticularis: androgens and some cortisol

3\.) zona fasciculata: cortisol and some androgens

4\.) zona glomerulosa: aldosterone

how are adrenal cortex hormones synthesize?

all are steroid hormones

precursor for all is cholesterol

p450 enzyme converts cholesterol to pregnenolone

pregnenolone to DHEA or progesterone

how is aldosterone synthesized?

progesterone to corticosterone to aldosterone

how is cortisol synthesized?

pregnenalone and progesterone to 17-hydroxyprogesterone to cortisol

how is androstenedione synthesized?

DHEA to androstenedione

can further make testosterone, estrone (estradiol)

what are the 3 categories of adrenal cortex hormones?

1\.) mineralcorticoids (aldosterone)

2\.) glucocorticoids (cortisol)

3\.) sex hormones (androgens)

what are mineralocorticoids?

aldosterone

secreted from zona glomerulosa

regulates sodium and potassium levels

what are glucocorticoids?

cortisol

secreted from zonae fasciculata and reticularis

regulates body’s response to stress

regulates metabolism

what are sex hormones?

andorgens

secreted from zonae fasciculata and reticularis

regulates reproductive function

what is aldosterones mechanism of action?

binds cytosolic receptor activating genes

causes sodium and potassium channels to insert into apical membrane

causes sodium potassium pumps to insert into basolateral membrane

activates proteins that enhance the opening of sodium and potassium channels on the apical membrane

what 2 things stimulate aldosterone?

1\.) high plasma potassium (hyperkalemia)

2\.) angiotensin 2 (from low blood pressure)

what is hyperaldosteronemia?

primary aldosteronism

excess aldosterone production

ex. Conn’s syndrome

hyperplasia of zona glomerulosa

results in hypertension, sodium retention, decreased potassium

How is cortisol released?

stress stimulates hypothalamus to release CRH

CRH stimulates the anterior pituitary to release ACTH

ACTH stimulates the adrenal cortex to secrete cortisol

what are the actions of glucocorticoids?

promote energy mobilization

required for GH secretion

maintain vessel responsiveness to catecholamines

adaptive response to stress

used clinically to inhibit inflammation and allergic responses (low doses) and for immune suppression (high dose)

what are the metabolic effects of cortisol on the liver, muscle and adipose tissue?

liver: gluconeogenesis

muscle: protein catabolism

adipose tissue: lipolysis

what is cushing’s syndrome

too much cortisol

causes weight gain, hypertension, hyperglycemia, and protein depletion in tissues

what is addison’s disease?

plasma levels of cortisol are chronically low

loss of adrenal cortical function

causes weakness, hypoglycemia, hypotension, poor stress tolerance

usually affects aldosterone too leading to sodium loss potassium retention causing heart arrythmias

how care catecholamines synthesized?

occurs in adrenal medulla

tyrosine to L-dopa using tyrosine hydroxylase

L-dopa to dopamine using aromatic-L-amino acid decarboxylase

dopamine to norepinephrine using dopamine beta-hydroxylase

norepinephrine to epinephrine using phenylethanolamine N-methyltransferase (PNMT)

what are the actions of epinephrine?

promotes energy mobilization (glycogen to glucose and fat to fatty acids)

cardiovascular changes (increase heart rate, force of heart contraction and cardiac output)

shunting of blood from gut and skin to muscles

causes bronchodilation

what is the clinical use of epinephrine?

counter act symptoms of anaphylactic shock

what is the storage vs functional names for carbohydrates, fats and proteins?

carbohydrates: glycogen (storage) and glucose (functional)

proteins: protein (storage) and amino acids (functional)

fats: triglycerides (storage) and fatty acids (functional)

what are features of the absorptive state?

3-4 hours following a meal

nutrients in bloodstream plentiful

glucose as primary fuel

what are features of the postabsorptive state?

between meals

energy stores must be mobilized

fatty acids are primary fuel

what is the absorptive state of carbohydrates?

glucose is the primary fuel

glycogen synthesis and storage (glycogenesis) in liver

conversion of excess glucose to triglycerides and storage in fat

what is the post absorptive state of carbohydrates?

glycogen breakdown (glycogenolysis)

glucose synthesized (gluconeogenesis)

what is the absorptive state of proteins?

protein synthesis

conversion of excess amino acids to triglycerides and storage as fat

what is the postabsorptive state of protein?

protein breakdown

amino acids used for gluconeogenesis by liver

what is the absorptive state of lipids?

triglyceride synthesis and storage (lipogenesis)

liver is also a site for fat synthesis

what is the postabsorptive state of lipids?

triglyceride breakdown (lipolysis) with lipoprotein lipase

fatty acids primary fuel

glycerol can be converted to glucose

fatty acids can be converted to ketones

what do pancreatic alpha cells vs beta cells secrete?

alpha: glucagon

beta: insulin

what is insulin?

peptide hormone

increased secretion during absorptive state

stimulated by increased glucose and amino acids in plasma, parasympathetic activity and incretins (GLP-1, GIP)

decreased secretion in postabsorptive state

inhibited by epinephrine and somatostatin

promotes anabolism

promotes glucose uptake by body cells

prevents liver from glucose output

what is the effects of increased plasma insulin on muscle, adipocytes and liver?

muscle: increase glucose uptake and utilization, net glycogen sythesis, aa uptake and protein synthesis

adipocytes: increase glucose uptake and utilization, net triglyceride synthesis

liver: decreased gluconeogenesis, net glycogen synthesis, triglyceride synthesis, no ketone synthesis

what is the effects of decreased plasma insulin on muscle, adipocytes and liver?

muscle: decrease glucose uptake and utilization, net glycogen catabolism, protein catabolism, amino acid release and fatty acid uptake and utilization

adipocytes: decrease glucose uptake and utilization, net triglyceride catabolism and release of glycerol and fatty acids

liver: increase glucose release due to removal of inhibitory effects on glycogen catabolism and gluconeogenesis, increase ketone synthesis and release

how does glucagon regulate glucose?

decreased plasma glucose stimulates alpha cells secreting glucagon

results in an increase in liver glycogenolysis, gluconeogenesis and ketone synthesis

ONLY ACTS ON LIVER AND ADIPOSE TISSUES